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ABSTRACT: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1.
Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe.
In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF.
These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.
British Journal of Dermatology 09/2006; 155(2):372-8. · 3.67 Impact Factor
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ABSTRACT: The aim of the present study was to determine the effect of AS-101, a known immunomodulator, on the pattern of cytokine production in children with patchy alopecia areata (PAA). Ten previously untreated children with PAA were compared to 10 healthy age- and sex-matched controls. Peripheral blood mononuclear cells (PBMC) were isolated from all participants. Unstimulated and phytohaemagglutinin (PHA)-stimulated PBMC were tested with and without the addition of AS-101. The production of interferon gamma (IFNgamma), soluble interleukin (IL)-2 receptor (IL-2R), IL-10, IL-5 and IL-6 was determined. The levels of soluble IL-2R, IL-5 and IL-6 were significantly higher in the PAA patients than the controls. AS-101 inhibited the production of IL-10, IFNgamma, IL-2R and IL-5 in both PAA patients and controls, but there was a greater inhibitory effect in children with PAA.
Clinical and Experimental Dermatology 08/2005; 30(4):432-4. · 1.20 Impact Factor
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ABSTRACT: The aetiology of mycosis fungoides (MF) and Sézary syndrome (SS) is unknown. A pathogenic role for the human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. We used an animal model to test the possibility that peripheral blood mononuclear cells (PBMC) obtained from MF patients harbour the HTLV-1 virus which may be infective. The polymerase chain reaction (PCR) was used to detect HTLV-1 proviral DNA sequences in PBMC of 27 MF patients and one SS patient of non-Iranian origin. Positive results were found in six of the patients. Twelve of the 28 patients tested by Western blot showed HTLV-1 antibodies. Twenty-eight immunosuppressed inbred Fisher F344 rats were inoculated intravenously with cultures of PBMC obtained from the 28 patients. Eight of these 28 rats showed antibodies to HTLV-1 while the proviral genome was demonstrated in the blood of only two of the rats. PBMC from two MF patients, in spite of showing negative results for the proviral genome by PCR, still induced HTLV-1 antibody formation in the F344 rat model. None of 10 control rats inoculated with normal donor PBMC showed antibodies to HTLV-1, nor the proviral genome. The present study suggests that HTLV-1 plays a cofactor role in MF/SS patients.
British Journal of Dermatology 08/1999; 141(1):44-9. · 3.67 Impact Factor
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M Shohat,
D Ben Amitai,
B Shohat,
R Mosberg,
R Narinski,
T Klein,
E Okon,
P Roizman,
E P Cowan,
R Alexander,
M David
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ABSTRACT: Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski's sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRB1* DQB1*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient's peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders.
Dermatology 02/1999; 199(4):356-60. · 2.05 Impact Factor
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ABSTRACT: In the present study, 63 specimens of human amniotic fluid were tested for the presence of free soluble interleukin-2 receptor (IL-2R). Thirty-two of these were also tested for the presence of IL-2. Significant reduction in free soluble IL-2R (IU/ml) or free IL-2R (IU/mg albumin) levels were found in the amniotic fluid obtained from pregnant women with Down's syndrome fetuses as compared with normal pregnancies. In addition normal amniotic fluid was found to contain low levels of IL-2, while no IL-2 was found in amniotic fluid from pregnant women with Down's syndrome fetuses when tested by two different tests.
Biology of the Neonate 02/1993; 63(5):281-4. · 1.90 Impact Factor
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ABSTRACT: We present 2 sibs with a local junctional type of epidermolysis bullosa associated with enamel defect of the teeth, dystrophic nails of the feet, and mental retardation. Subluxation of the lenses was evident in 1 of them. This combination found in a brother and a sister seems to represent a distinct autosomal recessive type of epidermolysis bullosa.
American Journal of Medical Genetics 08/1992; 43(5):776-9.
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ABSTRACT: Cytokines are known to play a major role in the pathogenesis of mycosis fungoides, a cutaneous malignant neoplasm of CD 4 T cells. In the present study, we investigated the effect of AS101, a tellurium-based compound with immunomodulating properties, on the pattern of lymphokine production by peripheral blood mononuclear cells (PBMCs) from patients with mycosis fungoides. PBMCs were isolated from 35 patients with mycosis fungoides stage IA and IB before initiation of treatment and from 20 healthy sex and age-matched controls. Unstimulated and phytohaemagglutinin-stimulated PBMCs were tested with and without the addition of AS101. The production of interferon-gamma, interleukin 2 (IL-2), IL-2 receptor (IL-2R), interleukin 5 (IL-5) and interleukin 10 (IL-10) was determined by enzyme-linked immunosorbent assays. The effects of AS-101 on mycosis fungoides PBMCs were compared to those of healthy donor PBMCs. Significantly higher levels of IL-2R, IL-5 and IL-10 and significantly lower levels of interferon-gamma were found in the patients compared to the controls. There was no significant difference between the groups in the production of IL-2. AS101 inhibited the production of IL-2R, IL-5 and IL-10 and induced a significant increase in IL-2 levels in the mycosis fungoides PBMCs. These findings may have important clinical implications for the possible therapeutic benefit of AS101 in mycosis fungoides.
Acta Dermato Venereologica 81(4):255-7. · 3.18 Impact Factor
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ABSTRACT: A study was undertaken to isolate pure human antisperm antibodies from the sera of infertile couples. One hundred infertile couples attending the Infertility and IVF Unit (Beilinson Medical Center) because of unexplained infertility were tested (both partners) for antisperm antibodies. Sixty-eight experiments were performed with positive sera containing antisperm antibodies and normal donor sperm. These experiments were followed by experiments in order to elute pure human antisperm antibodies from the sperm surface. Three experiments were performed with human sperm which were found to be coated by antisperm antibodies, in order to directly elute these antibodies from the sperm surface. In all experiments we eluted antisperm antibodies of the IgG and IgA isotypes from the sperm surface. These antibodies were demonstrated in the eluate, in each case by either the indirect immunobead test, the radial immune diffusion assay, or the electrophoresis method. Control experiments were performed as follows: (i) normal donor sperm incubated with normal serum; (ii) normal donor sperm without serum incubation; (iii) normal donor lymphocytes incubated with serum containing antisperm antibodies; (iv) normal donor lymphocytes without serum incubation. No antisperm antibodies were obtained in any of these control experiments. Absorption and elution experiments can be used for the isolation of pure human antisperm antibodies, which may then be used for the production of anti-idiotypic antibodies to antisperm antibodies. The anti-idiotypic antibodies could be further utilized as antigen substitutes for the production of a contraceptive vaccine and/or for application in the treatment of spontaneous abortion and infertility.
Andrologia 28(5):275-9. · 1.55 Impact Factor